An increased frequency of cancer has been reported for the heterozygous carriers of the genes for Fanconi anemia and ataxia-telangiectasia, autosomal recessive diseases which carry a high malignancy risk for homozygotes. We are evaluating the risk of developing cancer in heterozygotes for two genetic conditions: carriers of balanced translocations and carriers of the protease inhibitor (alpha 1-antitrypsin) allele Pi Z and/or other abnormal alleles. Members of families in which chromosomal translocations are segregating will be karyotyped using quinacrine fluorescence, trypsin-Giemsa banding and reverse banding. Members of families in which heterozygosity for Pi alleles has been identified will be Pi typed with isoelectric focusing, acid starch gel electrophoresis and crossed immunoelectrophoresis. Detailed family histories will be obtained. Pedigrees will be analyzed for an increase in cancer in proven or probable carriers. Thirty-five translocation families and 100 Pi families will be studied. The family data will be compared to U.S. mortality statistics. Families with an increased incidence of cancer will be HLA typed to identify any association of haplotype with malignancy. Pi families will also be analyzed for possible associations of haplotype with other diseases whose development may be related to alpha 1-antitrypsin deficiency. In addition to defining the frequency of neoplasia in these conditions, we hope to identify any factors which may influence the development of disease in individuals at risk due to their genotypes.